Efficacy and Safety of Ursodeoxycholic Acid (UDCA) Added to the DPP-4 Inhibitor in People With Type 2 Diabetes and Chronic Liver Diseases

• Status: Unknown status
• Trial end date: 2013-03-01
• Target enrollment: 0
• Participant gender: All

Summary

1. Objectives

1. To test whether Ursodeoxycholic Acid (UDCA) increases Glucagon-like peptide-1 (GLP-1) response to nutrients and improves glycemic control in people with type 2 diabetes.

2. To test whether sitagliptin enhances UDCA-induced beneficial effect in GLP-1 levels and glycemic control.

3. To test safety of combination therapy of sitagliptin and UDCA in people with type 2 diabetes.

2. Clinical hypothesis.

1. UDCA increases GLP-1 response to nutrients via provoking bile acids excretion from the liver to the intestine/colon.

2. UDCA improves glycemic control in people with type 2 diabetes.

3. Sitagliptin enhances UDCA-induced response of GLP-1 to nutrients.

4. Sitagliptin has additive beneficial effects with UDCA in glycemic control in people with type 2 diabetes.

5. Combination therapy of sitagliptin and UDCA is safe and well-tolerated in people with type 2 diabetes.

6. The combination therapy may loose weight by unique mechanisms of each agent; GLP-1 inhibits appetite by acting on CNS and gastrointestinal motility, whereas UDCA-enhanced circulating primary bile acids increases energy expenditure through the pathway involving G protein-coupled bile acid receptor 1 (Gpbar1, or M-Bar, TGR-5) and subsequent activation of type 2 iodothyronine deiodinase (D2) in brown adipose and muscle tissues, as reported previously.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kanazawa University
• Treatments: Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate; Ursodeoxycholic Acid

Criteria

Inclusion Criteria:

1. Type 2 diabetes

2. HbA1c >=6.5% during 8 weeks prior to the study

3. Treated with none or single oral hypoglycemic agent(OHA: sulfonyl ureas, biguanides, or thiazolidinediones) over 12 weeks prior to the study

Exclusion Criteria:

1. Non-Type 2 diabetes

2. Medical history and/or complication of diabetic ketoacidosis

3. Medical history and/or complication of severe hypoglycemia

4. Insulin treatment within 16 weeks prior to the study

5. Treatment with alpha-glucosidase inhibitors or sitagliptin within 12 weeks prior to the study

6. Treatment with glucocorticoid

7. Unstable glycemic control

8. Hypersensitivity to or contraindication of sitagliptin and voglibose

9. Aspartate transaminase (AST) or alanine transaminase (ALT) >=2.5 time of institutional upper normal limit

10. Uncontrolled hypertension (systolic blood pressure >160mmHg or diastolic blood pressure >100mmHg)

11. Severe health problems not suitable for the study

12. Pregnant or lactating women

13. Hepatitis B or C